THE IMMUNOLOGICAL BACKGROUND TO TRANSPLANTATION

Organs are transplanted clinically to rectify an irreversible function al deficit but, unless donor and recipient are genetically identical, graft antigens will trigger a rejection response by the recipient. In the early part of this century, experiments on transplantation of tumo urs showed that there were strict limitations on the ability of tumour grafts to survive. These 'laws of transplantation' were confirmed by the elegant work of Sir Peter Medawar and colleagues who also showed t hat rejection is a systemic process governed by lymphocytes. The study of skin graft rejection in mice led to the discovery of the major his tocompatibility complex (MHC) antigens, the function of which is to bi nd processed antigens and present them to T lymphocytes. T lymphocytes are pivotal in transplant rejection. The sensitization phase of rejec tion is due mainly to passenger leucocytes in the graft being recognis ed as foreign by the recipient's CD4(+) T cells. The effector phase of rejection involves these activated recipient T cells entering the gra ft and locally producing cytokines. The rate of rejection depends on t he relative contribution of the underlying immunological effector mech anisms. Our understanding of the role of T cells in transplant rejecti on has contributed much to knowledge on T cell physiology and function . The need to prevent rejection has also led to the development and us e of new immunomodulating agents, approaches which have implications i n the treatment of many other immunological disorders.